This project will study human complement components, immunoconglutinins (IK), and complement receptors on human leukocytes for their capacity to modify the actions of DNA/antiDNA immune complexes on antibody production in vitro. It aims to define a novel immunoregulatory role of complement, immunoconglutinins and complement receptors, individually and jointly, as intermediaries or modifiers of the interaction of immune complexes with leukocytes. This will be investigated by reconstitution in vitro of the normal human cellular network involved in antibody synthesis, introduction of immune complexes of defined biochemical composition into this system, and quantitation of the resulting effects on immunoglobulin production. The emphasis will be placed on quantitative analyses of interactions among purified, human immunochemical and cellular reagents in order to pinpoint sites and mechanisms of action at a molecular level. The study will incorporate technology arising from major recent advances in immunology including purification of complement and complement control proteins and understanding of their interactions, isolation of IK's with specificity for particular complement activation products, definition and isolation of various complement receptors on different leukocyte subpopulations, understanding of the role of interleukens in control of antibody synthesis, and identification and separation of subpopulations of leukocytes using the fluorescence-activated cell sorter along with monoclonal antibody technology. Although the study uses pathogenic immune complexes most relevant to the human disease system lupus erythematosus (SLE), it may also provide insights into normal regulation of antibody synthesis, particularly since only reagents from human sources will be used.